We have cloned four different human p21 ras genes which are homologous to the p21 transforming genes of Harvey and Kirsten murine sarcoma viruses. Chromosomal mapping of these genes has demonstrated that they are dispersed to four different chromosomes. An activated form of one of these genes has been found to be a tumor oncogene. The highly oncogenic property of this activated gene has been localized by genetic studies and by DNA sequence analysis to a point mutation in the p21 coding region of the gene. Since elevated levels of the normal p21 protein encoded by this gene can also be oncogenic, these results indicate that p21 ras genes can be oncogenic by either of two mechanisms: increased levels of the normal gene product or normal levels of a structurally altered gene product. Papillomavirus research has been both basic and applied. The capacity of Bovine papillomavirus (BPV) DNA to transform mouse cells has been studied. The sequences responsible for transformation by BPV are not identical to those required for its maintenance as a multiple copy extra-chromosomal element. A 2.3 kb segment of the viral DNA which cannot by itself induce transformation can be activated by a retroviral LTR to be transforming. Cells transformed by such a construction contain integrated copies of the viral DNA. The demonstration that cells transformed by Bovine papillomavirus can be cured of their viral DNA by long term treatment with interferon has been applied clinically to a trial of human leukocyte interferon in patients with epidermodysplasia verruciformis, a disease of chronic widespread wart virus infection. In short term studies, intralesional or systemic treatment with human leukocyte interferon resulted in a marked diminution in the size of warts and a decrease in the number of virus-positive cells in lesional skin.